Subfamily Coleoscirinae (Acari: Trombidiformes: Cunaxidae), with description of one new species from Pakistan.
The Coleoscirinae (Acari: Trombidiformes: Cunaxidae) from Pakistan are summarized in this paper. Two species of Scutascirus Den Heyer (S. pirgus Chaudhri and Akbar and S. tactus Chaudhri and Akbar), ten species of Coleoscirus Berlese (C. baptos (Chaudhri and Akbar), C. carex (Inayatullah and Shahid), C. carnus Muhammad and Chaudhri, C. comis Muhammad and Chaudhri, C. disparis Muhammad and Chaudhri, C. irroratus Muhammad and Chaudhri, C. mardi (Inatullah and Shahid), C. raviensis Afzal, Ashfaq and Khan, C. tobaensis Bashir, Afzal, Ashfaq, and Khan, and C. trudus Bashir, Afzal and Akbar), and three species of Pseudobonzia Smiley (P. ashfaqi Bashir, Afzal and Akbar, P. numida Chaudhri and Akbar, and P. parilus Chaudhri) have been previously reported. One new species of Pseudobonzia, Pseudobonzia bakeri sp n., is herein described and illustrated. A key to the genera of the subfamily and keys to the species in each genus are given to incorporate the new species from Pakistan. Distribution records of all known species in Pakistan are also given.


Antifibrotic role of αB-crystallin inhibition in pleural and subpleural fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by myofibroblast proliferation and extracellular-matrix accumulation. IPF typically starts in subpleural lung regions, and recent studies suggest that pleural mesothelial cells play a role in the onset of the disease. The transition of mesothelial cells into myofibroblasts (mesothelio-mesenchymal transition) is induced by the profibrotic cytokine, transforming growth factor (TGF)-β1, and is thought to play a role in the development and progression of IPF. The Mothers Against Decapentaplegic homolog (Smad)-dependent pathway is the main TGF-β1 pathway involved in fibrosis. αB-crystallin is constitutively expressed in the lungs, and is inducible by stress, acts as a chaperon, and is known to play a role in cell cytoskeleton architecture. We recently showed that the lack of αB-crystallin hampered TGF-β1 signaling by favoring Smad4 monoubiquitination and nuclear export. We demonstrate here, for the first time, that αB-crystallin is strongly overexpressed in the pleura of fibrotic lungs from patients with IPF and in rodent models of pleural/subpleural fibrosis. αB-crystallin-deficient mice are protected from pleural/subpleural fibrosis induced by the transient adenoviral-mediated overexpression of TGF-β1 or the intrapleural injection of bleomycin combined with carbon particles. We show that αB-crystallin inhibition hampers Smad4 nuclear localization in pleural mesothelial cells and the consequent characteristics of mesothelio-mesenchymal transition. αB-crystallin-deficient mesothelial cells fail to acquire the properties of myofibroblasts, thus limiting their migration in vivo and the progression of fibrosis in the lung parenchyma. In conclusion, our work demonstrates that αB-crystallin may be a key target for the development of specific drugs in the treatment of IPF.


Quantitative assessment of solid waste treatment systems in the industrial ecology perspective by exergy analysis.
Solid waste treatment options (recycling, incineration, and landfilling; the two latter processes both with co-generation of heat and electricity) have been studied for cardboard, newspaper, polyethylene, poly(ethylene terephthalate), polypropylene, polystyrene, and poly(vinyl chloride) waste. The conversion processes have been analyzed in terms of the second law of thermodynamics. The analysis allows calculating the exergy (useful energy) embodied in conversion products that can be obtained from the required inputs for the treatment processes. Taking into account the waste materials and the resources to convert them, it proved that recycling is the most efficient option for polyethylene with an efficiency of 62.5% versus 43.6% for incineration and 0.9% for landfilling. Next, waste treatment has been put into the broader perspective of industrial ecology. Exergetic efficiencies of industrial metabolic options have been calculated. Here resources for manufacturing and converting solid products have been considered. Furthermore, selection of one type of conversion excludes the generation of other potential conversion products. Therefore, it has to be taken into account that these latter products still have to be produced starting from virgin resources. Recycling proved to be the most efficient strategy: the ratio eta between exergy embodied in all delivered products on one hand, and all exergy withdrawn from the ecosphere or from waste materials on the other hand, is the highest. For polyethylene, eta proved to be 0.568, whereas eta is 0.503 and 0.329 for incineration and landfilling, respectively. On the other hand, if R the ratio between exergy of delivered products on one hand and exergy of virgin materials on the other hand is calculated, the differences between the industrial metabolic options are larger. Recycling polyethylene showed a ratio R of 0.936, whereas ratios of 0.772 and 0.531 were found for incineration and landfilling, respectively. It has been shown that the exergy concept allows a quantitative comparison of different industrial metabolic options, contributing to a better assessment of sustainability of technology with respect to resource management.


Localization of ribosomal protein S1 in the granular component of the interphase nucleolus and its distribution during mitosis.
Using antibodies to various nucleolar and ribosomal proteins, we define, by immunolocalization in situ, the distribution of nucleolar proteins in the different morphological nucleolar subcompartments. In the present study we describe the nucleolar localization of a specific ribosomal protein (S1) by immunofluorescence and immunoelectron microscopy using a monoclonal antibody (RS1-105). In immunoblotting experiments, this antibody reacts specifically with the largest and most acidic protein of the small ribosomal subunit (S1) and shows wide interspecies cross-reactivity from amphibia to man. Beside its localization in cytoplasmic ribosomes, this protein is found to be specifically localized in the granular component of the nucleolus and in distinct granular aggregates scattered over the nucleoplasm. This indicates that ribosomal protein S1, in contrast to reports on other ribosomal proteins, is not bound to nascent pre-rRNA transcripts but attaches to preribosomes at later stages of rRNA processing and maturation. This protein is not detected in the residual nucleolar structures of cells inactive in rRNA synthesis such as amphibian and avian erythrocytes. During mitosis, the nucleolar material containing ribosomal protein S1 undergoes a remarkable transition and shows a distribution distinct from that of several other nucleolar proteins. In prophase, the nucleolus disintegrates and protein S1 appears in numerous small granules scattered throughout the prophase nucleus. During metaphase and anaphase, a considerable amount of this protein is found in association with the surfaces of all chromosomes and finely dispersed in the cell plasm. In telophase, protein S1-containing material reaccumulates in granular particles in the nucleoplasm of the newly formed nuclei and, finally, in the re-forming nucleoli. These observations indicate that the nucleolus-derived particles containing ribosomal protein S1 are different from cytoplasmic ribosomes and, in the living cell, are selectively recollected after mitosis into the newly formed nuclei and translocated into a specific nucleolar subcompartment, i.e., the granular component. The nucleolar location of ribosomal protein S1 and its rearrangement during mitosis is discussed in relation to the distribution of other nucleolar proteins.


The integrity of cholinergic basal forebrain neurons depends on expression of Nkx2-1.
The transcription factor Nkx2-1 belongs to the homeobox-encoding family of proteins that have essential functions in prenatal brain development. Nkx2-1 is required for the specification of cortical interneurons and several neuronal subtypes of the ventral forebrain. Moreover, this transcription factor is involved in migratory processes by regulating the expression of guidance molecules. Interestingly, Nkx2-1 expression was recently detected in the mouse brain at postnatal stages. Using two transgenic mouse lines that allow prenatal or postnatal cell type-specific deletion of Nkx2-1, we show that continuous expression of the transcription factor is essential for the maturation and maintenance of cholinergic basal forebrain neurons in mice. Notably, prenatal deletion of Nkx2-1 in GAD67-expressing neurons leads to a nearly complete loss of cholinergic neurons and parvalbumin-containing GABAergic neurons in the basal forebrain. We also show that postnatal mutation of Nkx2-1 in choline acetyltransferase-expressing cells causes a striking reduction in their number. These degenerative changes are accompanied by partial denervation of their target structures and results in a discrete impairment of spatial memory.


Predicting the Fine Particle Fraction of Dry Powder Inhalers Using Artificial Neural Networks.
Dry powder inhalers are increasingly popular for delivering drugs to the lungs for the treatment of respiratory diseases, but are complex products with multivariate performance determinants. Heuristic product development guided by in vitro aerosol performance testing is a costly and time-consuming process. This study investigated the feasibility of using artificial neural networks (ANNs) to predict fine particle fraction (FPF) based on formulation device variables. Thirty-one ANN architectures were evaluated for their ability to predict experimentally determined FPF for a self-consistent dataset containing salmeterol xinafoate and salbutamol sulfate dry powder inhalers (237 experimental observations). Principal component analysis was used to identify inputs that significantly affected FPF. Orthogonal arrays (OAs) were used to design ANN architectures, optimized using the Taguchi method. The primary OA ANN r2 values ranged between 0.46 and 0.90 and the secondary OA increased the r2 values (0.53-0.93). The optimum ANN (9-4-1 architecture, average r2 0.92 ± 0.02) included active pharmaceutical ingredient, formulation, and device inputs identified by principal component analysis, which reflected the recognized importance and interdependency of these factors for orally inhaled product performance. The Taguchi method was effective at identifying successful architecture with the potential for development as a useful generic inhaler ANN model, although this would require much larger datasets and more variable inputs.


Optimizing oral nutritional drink supplementation in patients with chronic obstructive pulmonary disease.
Nutritional support is indicated in some patients with chronic obstructive pulmonary disease to restore nutritional status and improve functional capacity. However, the efficacy of nutritional supplements is sometimes disappointing, partly owing to a compensatory drop in habitual food intake. We retrospectively studied the effect of nutritional drink supplements, differing in portion size and energy content, on weight gain and body composition. Thirty-nine patients with stable chronic obstructive pulmonary disease, participating in an 8-week pulmonary rehabilitation programme and eligible for nutritional support, were studied. Group A (n 19) received three portions of 125 ml (2380 kJ), whereas group B (n 20) received three portions of 200 ml (3350 kJ) daily. The macronutrient composition of the regimens was similar (20 % protein, 60 % carbohydrates and 20 % fat). Lung function, body weight, body composition (by bio-electrical impedance analysis), habitual dietary intake (by dietary history) and resting energy expenditure (by ventilated hood) were determined. Weight gain was compared with expected weight as predicted by a computer simulation model. Although patients in both groups significantly increased in weight, this increase was higher in group A (A, 3.3 (sd 1.9) kg; B, 2.0 (sd 1.2) kg; P=0.019), while receiving less energy. The observed weight gain in group A was similar to that expected, but in group B it was lower than expected (P<0.001). In both groups, fat-free mass and fat mass were gained in a ratio of 2:1, fat-free mass increasing primarily during the first 4 weeks. This study illustrates that there might be an optimum for the portion size of nutritional drink supplements in chronic obstructive pulmonary disease and that more is not always better.


Imaging of gliomas at 1.5 and 3 Tesla - A comparative study.
Glioma follow-up is based on MRI parameters, which are correlated with survival. Although established criteria are used to evaluate tumor response, radiological markers may be confounded by differences in instrumentation including the magnetic field strength. We assessed whether MRIs obtained at 3 Tesla (T) and 1.5T provided similar information. We retrospectively compared imaging features of 30 consecutive patients with WHO grades II and III gliomas who underwent MRI at 1.5T and 3T within a month of each other, without any clinical changes during the same period. We compared lesion volumes on fluid attenuation inversion recovery (FLAIR), ratio of cerebral blood volume (rCBV) on perfusion-weighted imaging, contrast-to-noise ratio (CNR) on FLAIR, and on post-gadolinium 3D T1-weighted sequences between 1.5T and 3T using intraclass correlation coefficient (ICC). Concordance between observers within and between modalities was evaluated using weighted-kappa coefficient (wκ). The mean ± SD delay between modalities (1.5T and 3T MRI) was 8.6 ± 5.6 days. Interobserver/intraobserver concordance for lesion volume was almost perfect for 1.5T (ICC = 0.96/0.97) and 3T (ICC = 0.99/0.98). Agreement between observers for contrast enhancement was excellent at 1.5T (wκ = 0.92) and 3T (wκ = 0.92). The tumor CNR was significantly higher for FLAIR at 1.5T (P < .001), but it was higher at 3T (P = .012) for contrast enhancement. Correlations between modalities for lesion volume (ICC = 0.97) and for rCBV values (ICC = 0.92) were almost perfect. In the follow-up of WHO grades II and III gliomas, 1.5T and 3T provide similar MRI features, suggesting that monitoring could be performed on either a 1.5 or a 3T MR magnet.


Cryo-EM structures provide insight into how E. coli F1Fo ATP synthase accommodates symmetry mismatch.
F1Fo ATP synthase functions as a biological rotary generator that makes a major contribution to cellular energy production. It comprises two molecular motors coupled together by a central and a peripheral stalk. Proton flow through the Fo motor generates rotation of the central stalk, inducing conformational changes in the F1 motor that catalyzes ATP production. Here we present nine cryo-EM structures of E. coli ATP synthase to 3.1-3.4 Å resolution, in four discrete rotational sub-states, which provide a comprehensive structural model for this widely studied bacterial molecular machine. We observe torsional flexing of the entire complex and a rotational sub-step of Fo associated with long-range conformational changes that indicates how this flexibility accommodates the mismatch between the 3- and 10-fold symmetries of the F1 and Fo motors. We also identify density likely corresponding to lipid molecules that may contribute to the rotor/stator interaction within the Fo motor.


Prospective study of predictors of attendance for breast screening in inner London.
To investigate the predictors of first-round attendance for breast screening in an inner city area. Prospective design in which women were interviewed or completed a postal questionnaire before being sent their invitation for breast screening. Sociodemographic factors, health behaviours, and attitudes, beliefs, and intentions were used as predictors of subsequent attendance. A randomised control group was included to assess the effect of being interviewed on attendance. Three neighbouring health districts in inner south east London. A total of 3291 women aged 50-64 years who were due to be called for breast screening for the first time. The analysis of predictors was based on a subsample of 1301, reflecting a response rate of 75% to interview and 36% to postal questionnaire. Attendance was 42% overall, and 70% in those who gave an interview or returned a questionnaire. There was little evidence for an interview effect on attendance. The main findings from the analysis of predictors are listed below. (These were necessarily based on those women who responded to interview/questionnaire and so may not be generalisable to the full sample.) (1) Sociodemographic factors: Women in rented accommodation were less likely to go for screening but other indicators of social class and education were not predictive of attendance. Age and other risk factors for breast cancer were unrelated to attendance, as was the distance between home and the screening centre. Married or single women were more likely to attend than divorced, separated, or widowed women, and black women had a higher than average attendance rate; however, neither of these relationships was found in the interview sample. (2) Health behaviours: Attenders were less likely to have had a recent breast screen, more likely to have had a cervical smear, more likely to go to the dentist for check ups, and differed from non-attenders with regard to drinking frequency. Exercise, smoking, diet change, and breast self-examination were unrelated to attendance. (3) Attitudes, beliefs, and intentions: The two best predictors were measures of the perceived importance of regular screening for cervical and breast cancer and intentions to go for breast screening. Also predictive were beliefs about the following: the personal consequences of going for breast screening, the effectiveness of breast screening, the chances of getting breast cancer, and the attitudes of significant others (the woman's husband/partner and children). Women who reported a moderate amount of worry about breast cancer were more likely to attend than those at the two extremes. Attenders and non-attenders differ in two broad areas: the health related behaviours they engage in and the attitudes, beliefs, and intentions they have towards breast cancer and breast screening. The latter are potentially amenable to change, and though different factors may operate among women who do not respond to questionnaires, the findings offer hope that attendance rates can be improved by targeting the relevant attitudes and beliefs. This could be done by changing the invitation letter and its accompanying literature, through national and local publicity campaigns, and by advice given by GPs, practice nurses, and other health professionals. It is essential that such interventions are properly evaluated, preferably in randomised controlled studies.


In vitro and in vivo activity of the low-immunogenic antimesothelin immunotoxin RG7787 in pancreatic cancer.
Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis, and new therapies are needed. RG7787 is a novel low-immunogenic antimesothelin recombinant immunotoxin (RIT), engineered to overcome the limitations of SS1P, a RIT now in clinical trials. In vitro activity was evaluated on five established PDAC cell lines (KLM-1, AsPC-1, BxPC-3, Panc 3.014, and PK-1) and on PDAC cells directly established from a patient tumor (GUMC108). RG7787 had subnanomolar IC50s in most cell lines, and was significantly more active than SS1P in GUMC108, KLM-1, and Panc 3.014 cells. GUMC108 was most sensitive, with RG7787 killing >99% of the cells. In a subcutaneous KLM-1 xenograft mouse model, two cycles of 3 × 2.5 mg/kg RG7787 QOD combined with two cycles of 1 × 50 mg/kg paclitaxel induced near-complete responses, with all tumors regressing below 5 mm(3) within 30 days after therapy was initiated (>95% decrease) and no significant growth increase for at least another 3 weeks. RG7787 alone gave limited but significant regressions and paclitaxel by itself arrested tumor growth. Quantifying the uptake of Alexa Fluor 647-labeled RG7787 in tumors showed that the RIT reached only 45% of KLM-1 cells, accounting in part for the limited responses. Paclitaxel did not improve RG7787 uptake, which thus cannot explain the beneficial effect of the combination therapy. In conclusion, RG7787 has high cytotoxic activity on PDAC cell lines as well as on primary patient cells. In vivo, this novel RIT gives durable near-complete tumor responses when combined with paclitaxel. RG7787 merits further evaluation for the treatment of PDAC.


HIV-1 drug resistance mutations emerging on darunavir therapy in PI-naive and -experienced patients in the UK.
Darunavir is considered to have a high genetic barrier to resistance. Most darunavir-associated drug resistance mutations (DRMs) have been identified through correlation of baseline genotype with virological response in clinical trials. However, there is little information on DRMs that are directly selected by darunavir in clinical settings. We examined darunavir DRMs emerging in clinical practice in the UK. Baseline and post-exposure protease genotypes were compared for individuals in the UK Collaborative HIV Cohort Study who had received darunavir; analyses were stratified for PI history. A selection analysis was used to compare the evolution of subtype B proteases in darunavir recipients and matched PI-naive controls. Of 6918 people who had received darunavir, 386 had resistance tests pre- and post-exposure. Overall, 2.8% (11/386) of these participants developed emergent darunavir DRMs. The prevalence of baseline DRMs was 1.0% (2/198) among PI-naive participants and 13.8% (26/188) among PI-experienced participants. Emergent DRMs developed in 2.0% of the PI-naive group (4 mutations) and 3.7% of the PI-experienced group (12 mutations). Codon 77 was positively selected in the PI-naive darunavir cases, but not in the control group. Our findings suggest that although emergent darunavir resistance is rare, it may be more common among PI-experienced patients than those who are PI-naive. Further investigation is required to explore whether codon 77 is a novel site involved in darunavir susceptibility.


Water on the sun: line assignments based on variational calculations.
The infrared spectrum of hot water observed in a sunspot has been assigned. The high temperature of the sunspot (3200 K) gave rise to a highly congested pure rotational spectrum in the 10-micrometer region that involved energy levels at least halfway to dissociation. Traditional spectroscopy, based on perturbation theory, is inadequate for this problem. Instead, accurate variational solutions of the vibration-rotation Schrödinger equation were used to make assignments, revealing unexpected features, including rotational difference bands and fewer degeneracies than anticipated. These results indicate that a shift away from perturbation theory to first principles calculations is necessary in order to assign spectra of hot polyatomic molecules such as water.


Three new species of Echinobothrium (Cestoda: Diphyllidea) from Indo-Pacific stingrays of the genus Pastinachus (Rajiformes: Dasyatidae).
Three new species of diphyllidean cestodes are described from stingrays of the genus Pastinachus from the Indian and Pacific Oceans. All three new species differ from all but 10 of the 36 valid species of Echinobothrium van Beneden, 1849 in that they bear lateral hooklets arranged in a continuous band across each lateral surface of the rostellum joining the groups of dorsal and ventral apical hooks, rather than arranged in distinct dorsal and ventral groups, on each side of the apical hooks. Echinobothrium nataliae sp. n. ex Pastinachus solocirostris off Borneo differs from other relatives in the following combination of characters: number of spines in each column on the cephalic peduncle, number of lateral hooklets and number of apical hooks. Echinobothrium reginae sp. n. ex Pastinachus cf. sephen off Madagascar differs from all congeners in the following combination of characters: number of hooklets and number of spines on the cephalic peduncle. Echinobothrium vojtai sp. n. from an undescribed species of Pastinachus off Borneo differs from its congeners in the following combination of characters: number of hooklets, number of apical hooks and number of spines in each column on the cephalic peduncle. The hook formula was modified to accommodate species with lateral hooklets arranged in a continuous band as follows: {(LH) AH(A)/AH(B)}, where (LH) is the total number of lateral hooklets in a band. A table of all nominal species of Echinobothrium, showing their taxonomic status, type host and locality, number of peduncle spines in a column and hook formula, is presented. Macrobothridium djeddensis and Macrobothridium sinensis are transferred to Echinobothrium. In addition, Echinobothrium deeghai is considered as a species inquirenda.


Immunopathology of adrenal and renal cortical tumors. Coordinated change in antigen expression is associated with neoplastic conversion in the adrenal cortex.
A series of adrenal cortical adenomas (ACA) and carcinomas (ACC), as well as normal adrenal cortex have been studied by a panel of 11 antibodies to characterize antigenic changes that may distinguish these morphologically similar entities. Normal adrenal cortex and ACA express low-molecular weight cytokeratin intermediate filaments. However, none of the six primary or seven metastatic ACCs were found to express detectable levels of cytokeratins. In contrast, vimentin was seen in all ACCs studied and was heterogeneously expressed by ACAs. However, its expression was usually confined to stromal elements of the normal adrenal cortex. We conclude that adrenal cortical cells undergo characteristic changes in intermediate filament expression during the process of neoplastic conversion and malignant transformation. Undetectable expression of cytokeratins and strong expression of vimentin is associated with malignant adrenal cortical lesions. In addition, we examined the antigenic phenotype of a series of primary renal cell carcinomas (RCC). Renal cell carcinomas express cytokeratins, while ACCs do not. The majority of primary RCCs express Lewis blood group isoantigens (most commonly Lewis X), while ACAs and ACCs do not. The panel of antibodies described here may help to distinguish morphologically similar lesions of like histogenesis (ACAs vs. ACCs) and lesions of different histogenesis (adrenal vs. renal) on the basis of their composite antigenic phenotypes.


Asymptomatic IgE mediated food hypersensitivity in patients with nasal polyps.
The aim of this prospective study is to compare the prevalence of atopy in patients afflicted by nasal polyps with the atopy prevalence in healthy volunteers without nasal polyps, since systemic allergy and allergy in the nasal mucosa are still being debated as underlying causes for nasal polyps. Thirty-four cases with nasal polyposis without asthma and history of allergy or atopic disease were enrolled in the study and compared with 20 healthy volunteer controls in respect to asymptomatic food hypersensitivity. Hypersensitivity for 48 kinds of commonly consumed food in Turkey was investigated by an epicutaneuos prick test, Multi-Test II (Lincoln Diagnostic, Inc, USA), using a special applicator. The food allergy test was positive in 25 out of the 34 cases with nasal polyps and in 6 out of the 20 controls. The difference between the two groups was statistically significant (chi2 = 0.000, p < 0.001). The number of skin tests with positive results in patients with nasal polyps ranged from 1 to 37 (mean +/- S.D. = 10.0 +/- 7.9), whereas in the control subjects the range was 1 to 10 (mean +/- S.D. = 4.0 +/- 3.3). The difference in the number of food reactions was also statistically significant. Asymptomatic food hypersensitivity, being immunologically mediated, may be a triggering factor for the pathogenesis of nasal polyps. Therefore, treatment of asymptomatic food allergy in patients with nasal polyps may alleviate symptoms, slow the progress of nasal polyps and prolong the disease-free interval after polypectomy.


Effects of vitamin/mineral supplementation on the prevalence of histological dysplasia and early cancer of the esophagus and stomach: results from the General Population Trial in Linxian, China.
A randomized nutrition intervention trial was conducted among 29,584 adult residents of Linxian, China, to examine the effects of vitamin/mineral supplementation on the occurrence of esophageal/gastric cardia cancer in this high-risk population. A fractional factorial study design allowed evaluations of four different combinations of nutrients: (A) retinol and zinc; (B) riboflavin and niacin; (C) vitamin C and molybdenum; and (D) beta-carotene, vitamin E, and selenium. During the 5.25-year intervention, significant reductions in total mortality, total cancer mortality, and stomach cancer mortality occurred among those receiving beta-carotene, vitamin E, and selenium. At the end of intervention, an endoscopic survey was carried out in a sample of subjects to see if the nutritional supplements had affected the prevalence of clinically silent precancerous lesions and early invasive cancers of the esophagus or stomach. Endoscopy was performed on 391 individuals from two study villages. The prevalences of esophageal and gastric dysplasia and cancer were compared by nutrient factor. Cancer or dysplasia was diagnosed in 15% of the participants. No statistically significant reductions in the prevalence of esophageal or gastric dysplasia or cancer were seen for any of the four vitamin/mineral combinations. The greatest reduction in risk (odds ratio, 0.38; P = 0.09) was seen for the effect of retinol and zinc on the prevalence of gastric cancer. Although no significant protective effects were seen in this endoscopic survey, there was a suggestion that supplementation with retinol and zinc may protect against the development of gastric neoplasia in this high-risk population. Additional studies with larger numbers of endpoints will be needed to further evaluate this possibility.


Associations between risk perceptions and worry about common diseases: a between- and within-subjects examination.
The relationships between worry and perceptions of likelihood and severity were evaluated across eight common diseases. Individual and disease variability in worry and perceptions were examined. 294 participants were recruited through the Multiplex Initiative, in which a genetic susceptibility test for eight common diseases was offered to healthy adults. Participants completed a baseline telephone survey and web-based surveys without a commitment to be tested, and then made a choice on testing. Between- and within-subjects analyses yielded the following main findings: (1) worry is more closely related to likelihood perceptions than to severity perceptions; (2) severity perceptions add significantly to explained worry variances above and beyond likelihood perceptions; (3) risk perceptions and worries form two clusters: cancer diseases and cardiovascular-metabolic diseases; and (4) variance in risk perception and worry is explained by a combination of between- and within-subjects variances. Risk perception research should attend to severity perceptions, within-subjects variability and inter-disease differences, and to strategies for grouping conditions.


Emerging applications of stimuli-responsive polymer materials.
Responsive polymer materials can adapt to surrounding environments, regulate transport of ions and molecules, change wettability and adhesion of different species on external stimuli, or convert chemical and biochemical signals into optical, electrical, thermal and mechanical signals, and vice versa. These materials are playing an increasingly important part in a diverse range of applications, such as drug delivery, diagnostics, tissue engineering and 'smart' optical systems, as well as biosensors, microelectromechanical systems, coatings and textiles. We review recent advances and challenges in the developments towards applications of stimuli-responsive polymeric materials that are self-assembled from nanostructured building blocks. We also provide a critical outline of emerging developments.


Machine learning from wristband sensor data for wearable, noninvasive seizure forecasting.
Seizure forecasting may provide patients with timely warnings to adapt their daily activities and help clinicians deliver more objective, personalized treatments. Although recent work has convincingly demonstrated that seizure risk assessment is in principle possible, these early approaches relied largely on complex, often invasive setups including intracranial electrocorticography, implanted devices, and multichannel electroencephalography, and required patient-specific adaptation or learning to perform optimally, all of which limit translation to broad clinical application. To facilitate broader adaptation of seizure forecasting in clinical practice, noninvasive, easily applicable techniques that reliably assess seizure risk without much prior tuning are crucial. Wristbands that continuously record physiological parameters, including electrodermal activity, body temperature, blood volume pulse, and actigraphy, may afford monitoring of autonomous nervous system function and movement relevant for such a task, hence minimizing potential complications associated with invasive monitoring and avoiding stigma associated with bulky external monitoring devices on the head. Here, we applied deep learning on multimodal wristband sensor data from 69 patients with epilepsy (total duration > 2311 hours, 452 seizures) to assess its capability to forecast seizures in a statistically significant way. Using a leave-one-subject-out cross-validation approach, we identified better-than-chance predictability in 43% of the patients. Time-matched seizure surrogate data analyses indicated forecasting not to be driven simply by time of day or vigilance state. Prediction performance peaked when all sensor modalities were used, and did not differ between generalized and focal seizure types, but generally increased with the size of the training dataset, indicating potential further improvement with larger datasets in the future. Collectively, these results show that statistically significant seizure risk assessments are feasible from easy-to-use, noninvasive wearable devices without the need of patient-specific training or parameter optimization.


Global and time-resolved monitoring of crop photosynthesis with chlorophyll fluorescence.
Photosynthesis is the process by which plants harvest sunlight to produce sugars from carbon dioxide and water. It is the primary source of energy for all life on Earth; hence it is important to understand how this process responds to climate change and human impact. However, model-based estimates of gross primary production (GPP, output from photosynthesis) are highly uncertain, in particular over heavily managed agricultural areas. Recent advances in spectroscopy enable the space-based monitoring of sun-induced chlorophyll fluorescence (SIF) from terrestrial plants. Here we demonstrate that spaceborne SIF retrievals provide a direct measure of the GPP of cropland and grassland ecosystems. Such a strong link with crop photosynthesis is not evident for traditional remotely sensed vegetation indices, nor for more complex carbon cycle models. We use SIF observations to provide a global perspective on agricultural productivity. Our SIF-based crop GPP estimates are 50-75% higher than results from state-of-the-art carbon cycle models over, for example, the US Corn Belt and the Indo-Gangetic Plain, implying that current models severely underestimate the role of management. Our results indicate that SIF data can help us improve our global models for more accurate projections of agricultural productivity and climate impact on crop yields. Extension of our approach to other ecosystems, along with increased observational capabilities for SIF in the near future, holds the prospect of reducing uncertainties in the modeling of the current and future carbon cycle.


Efficient transmission of crossing dielectric slot waveguides.
Transmission properties of two crossing dielectric slot waveguides (Si-Air-Si) are investigated using the finite difference in time domain method. Results show that the low transmission of this system mainly results from the reflection and radiation loss rather than the crosstalk. Using a simple method of filling up the crossing slots locally, the reflection, radiation losses and crosstalk are all greatly suppressed. With moderate parameters in this paper, the transmission efficient increases from 35.0% to more than 97% in a wide range of wavelength around 1.55 mm. The results and method presented in this paper may be very useful in the application of slot waveguide in micro and nano photonics.


Genome-wide analysis of genes targeted by PHYTOCHROME INTERACTING FACTOR 3-LIKE5 during seed germination in Arabidopsis.
PHYTOCHROME INTERACTING FACTOR 3-LIKE5 (PIL5) is a basic helix-loop-helix transcription factor that inhibits seed germination by regulating the expression of gibberellin (GA)- and abscisic acid (ABA)-related genes either directly or indirectly. It is not yet known, however, whether PIL5 regulates seed germination solely through GA and ABA. Here, we used Chromatin immunoprecipitation-chip (ChIP-chip) analysis to identify 748 novel PIL5 binding sites in the Arabidopsis thaliana genome. Consistent with the molecular function of PIL5 as a transcription regulator, most of the identified binding sites are located in gene promoter regions. Binding site analysis shows that PIL5 binds to its target sites mainly through the G-box motif in vivo. Microarray analysis reveals that phytochromes regulate a large number of genes mainly through PIL5 during seed germination. Comparison between the ChIP-chip and microarray data indicates that PIL5 regulates 166 genes by directly binding to their promoters. Many of the identified genes encode transcription regulators involved in hormone signaling, while some encode enzymes involved in cell wall modification. Interestingly, PIL5 directly regulates many transcription regulators of hormone signaling and indirectly regulates many genes involved in hormone metabolism. Taken together, our data indicate that PIL5 inhibits seed germination not just through GA and ABA, but also by coordinating hormone signals and modulating cell wall properties in imbibed seeds.


Association between statins and infections among patients with diabetes: a cohort and prescription sequence symmetry analysis.
A previous meta-analysis of randomized trials did not confirm findings from observational studies that suggested that statins reduce the risk of infection. However, animal experiments indicate that statins may be more effective in reducing the risk and/or the severity of infection among patients with diabetes. Hence, we evaluated the effect of statins on antibiotic prescriptions (a proxy for infections) among patients with drug-treated type 2 diabetes using two confounding-reducing observational designs. We conducted a prescription sequence symmetry analysis and a cohort study using the IADB.nl pharmacy prescription database. For the prescription sequence symmetry analysis, a sequence ratio was calculated. The matched cohort study, comparing the time to first antibiotic prescription between periods that statins are initiated and non-use periods, was analyzed using stratified Cox regression. Prescription sequence symmetry analysis of 4684 patients with drug-treated type 2 diabetes resulted in an adjusted sequence ratio of 0.86 (95% confidence interval [CI]: 0.81 to 0.91). Corresponding figures for the cohort analysis comparing 9852 statin-initiation with 4928 non-use periods showed similar results (adjusted hazard ratio: 0.88, 95%CI: 0.83 to 0.95). These findings suggest that statins are associated with a reduced risk of infections among patients with drug-treated type 2 diabetes. © 2016 The Authors. Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd.


Folinic acid protects against suppression of growth by methotrexate in mice.
The objective of this study was to investigate whether folinic acid supplementation would protect young mice against suppression of growth by methotrexate (MTX). Four equal groups of Balb/c young male mice (5 animals in each group; mean+/-SD body weight 9.64+/-0.85 g, in their rapid growth phase) were subjected to the following drug treatment: One group was given MTX (3.5 mg/kg body weight) intraperitoneally on every 2nd day, another received folinic acid (7.0 mg/kg body weight) intraperitoneally every 2nd day. The third group was given both of these drugs (MTX on every 2nd day and folinic acid 8 h post-MTX injection). The fourth group was injected with physiological saline every other day to serve as a control group. Total body weight, food and water consumption by animals in each group were monitored every second day for a period of 3 weeks. After this period mice were sacrificed and liver, spleen and kidneys were excised, weighed and analyzed for MTX and dihydrofolate reductase activity. A small segment of the proximal part of small intestine and small pieces of liver and kidney were also removed to study morphological changes. Compared to the groups, which received folinic acid alone, folinic acid plus MTX or physiological saline, mean increase in body weight (6.8+/-0.8 g) of mice over a period of 3 weeks was minimal in the group receiving MTX alone (one-way ANOVA p=0.0001). The mean weights of liver and kidney in this group receiving MTX alone were also found to be significantly less than the mean weights of these organs in the 3 groups (p<0.001). The negative effect on growth of animals appears not only due to malabsorption but inhibition of pathway of de novo DNA synthesis may also be involved. This is supported by loss of villous pattern in small intestine of mice treated with MTX alone and increased accumulation of free MTX and decreased dihydrofolate reductase in the liver of the group receiving MTX alone as compared with the group receiving MTX plus folinic acid. The data indicate that the administration of folinic acid protects mice against suppression of growth by MTX. On the basis of these observations it can be deduced that patients suffering from juvenile rheumatoid arthritis or acute lymphoblastic leukaemia receiving MTX over a long period of time might be at a risk of experiencing short-term suppression of growth, however they could benefit from supplementation with folinic acid.


Educating Pharmacists in Quality (EPIQ): Recipient, Academy for Healthcare Improvement 2015 Duncan Neuhauser Award for Curricular Innovation.
The Duncan Neuhauser Award for curriculum Innovation is presented annually at the Academy for Healthcare Improvement meeting. The award recognizes education providers that show innovation and improvement in advancing skills in health care. Duncan B. Neuhauser, PhD, a Senior Editor with the Quality Management in Health Care journal is a Professor of Health Services Research and the Charles Elton Blanchard Professor of Health Management at Case Western Reserve University. Dr Neuhauser has devoted his working life to the science of the improvement of health care and has served as a pioneer in the development of curriculum to promote health care improvement. The 2015 first place recipient was Educating Pharmacists in Quality (EPIQ) developed by the Pharmacy Quality Alliance. EPIQ was developed as a quality improvement education resource for use by pharmacy faculty and other professionals to teach students pharmacists, pharmacists, and other stakeholders about measuring, reporting, and improving quality in pharmacy practice. EPIQ has been integrated into more than 20 doctor of pharmacy curricula and has been used as part of employee training programs. Students and faculty members who have used the program have indicated via surveys that the program has a positive impact on awareness and knowledge of quality improvement in pharmacy.


Characteristics of a femtosecond transform-limited Kerr-lens mode-locked dye laser.
Using an SF6 glass plate as the intracavity Kerr medium and a double-prism pair for dispersion compensation, we developed a femtosecond transform-limited passively mode-locked dye laser. Self-starting mode locking is achieved with a dilute intracavity TCVEBI saturable-absorber jet. Within a 50% power drop the tuning range is 577-606 nm. Pulse characteristics of the laser agree with theoretical predictions based on the Ginzburg-Landau equation.


Synthesis and release of trace elements from hollow and porous hydroxyapatite spheres.
It is known that organic species regulate fabrication of hierarchical biological forms via solution methods. However, in this study, we observed that the presence of inorganic ions plays an important role in the formation and regulation of biological spherical hydroxyapatite formation. We present a mineralization method to prepare ion-doped hydroxyapatite spheres with a hierarchical structure that is free of organic surfactants and biological additives. Porous and hollow strontium-doped hydroxyapatite spheres were synthesized via controlling the concentration of strontium ions in a calcium and phosphate buffer solution. Similarly, fluoride and silicon-doped hydroxyapatite spheres were synthesized. While spherical particle formation was attainable at low and high temperature for Sr-doped hydroxyapatite, it was only possible at high temperature in the F/Si-doped system. The presence of inorganic ions not only plays an important role in the formation and regulation of biological spherical hydroxyapatite, but also could introduce pharmaceutical effects as a result of trace element release. Such ion release results showed a sustained release with pH responsive behavior, and significantly influenced the hydroxyapatite re-precipitation. These ion-doped hydroxyapatite spheres with hollow and porous structure could have promising applications as bone/tooth materials, drug delivery systems, and chromatography supports.


The tail domain of myosin Va modulates actin binding to one head.
Calcium activates full-length myosin Va steady-state enzymatic activity and favors the transition from a compact, folded "off" state to an extended "on" state. However, little is known of how a head-tail interaction alters the individual actin and nucleotide binding rate and equilibrium constants of the ATPase cycle. We measured the effect of calcium on nucleotide and actin filament binding to full-length myosin Va purified from chick brains. Both heads of nucleotide-free myosin Va bind actin strongly, independent of calcium. In the absence of calcium, bound ADP weakens the affinity of one head for actin filaments at equilibrium and upon initial encounter. The addition of calcium allows both heads of myosin Va.ADP to bind actin strongly. Calcium accelerates ADP binding to actomyosin independent of the tail but minimally affects ATP binding. Although 18O exchange and product release measurements favor a mechanism in which actin-activated Pi release from myosin Va is very rapid, independent of calcium and the tail domain, both heads do not bind actin strongly during steady-state cycling, as assayed by pyrene actin fluorescence. In the absence of calcium, inclusion of ADP favors formation of a long lived myosin Va.ADP state that releases ADP slowly, even after mixing with actin. Our results suggest that calcium activates myosin Va by allowing both heads to interact with actin and exchange bound nucleotide and indicate that regulation of actin binding by the tail is a nucleotide-dependent process favored by linked conformational changes of the motor domain.


Establishing Medical Schools in Limited Resource Settings.
One urgent goal of countries in sub-Saharan Africa is to dynamically scale up the education and work force of medical doctors in the training institutions and health facilities, respectively. These countries face challenges related to the rapid scale up which is mostly done without proper strategic planning, without the basic elements of infrastructure development, educational as well as academic and administrative human resources. Medical education done in the context of limited resources is thus compromising the quality of graduates. In the future, a collaborative and need-based approach involving major stakeholders such as medical educators concerned, ministries, planners and policy makers is needed. This article identifies the challenges of establishing medical schools and sustaining the quality of education through rapid scale-up in Sub-Saharan Africa in the settings of limited resources. It also outlines the minimum requirements for establishing medical schools. A consensus building workshop was conducted in Bishoftu, Ethiopia, from Nov 8-12, 2013. Participants were professionals from 13 Ethiopian medical schools, and representatives of medical schools from South Sudan, Somaliland, Somalia, and Mozambique. Participants are listed in Appendix 1. The governments and stakeholders should jointly develop strategic plans and a roadmaps for opening or expanding medical schools to scale up educational resources. It is advisable that medical schools have autonomy regarding the number of student-intake, student selection, curriculum ownership, resource allocation including for infrastructure and staff development. Health science and medical curricula should be integrated within and harmonized nationally. An educational evaluation framework needs to be embedded in the curricula, and all medical schools should have Health Science Education Development Centers.


TRELLIS+: an effective approach for indexing genome-scale sequences using suffix trees.
With advances in high-throughput sequencing methods, and the corresponding exponential growth in sequence data, it has become critical to develop scalable data management techniques for sequence storage, retrieval and analysis. In this paper we present a novel disk-based suffix tree approach, called TRELLIS+, that effectively scales to massive amount of sequence data using only a limited amount of main-memory, based on a novel string buffering strategy. We show experimentally that TRELLIS+ outperforms existing suffix tree approaches; it is able to index genome-scale sequences (e.g., the entire Human genome), and it also allows rapid query processing over the disk-based index. TRELLIS+ source code is available online at http://www.cs.rpi.edu/-zaki/software/trellis


The influence of goal-state access cost on planning during problem solving.
Two problem-solving experiments investigated the relationship between planning and the cost of accessing goal-state information using the theoretical framework of the soft constraints hypothesis (Gray & Fu, 2004; Gray, Simms, Fu, & Schoelles, 2006). In Experiment 1, 36 participants were allocated to low, medium, and high access cost conditions and completed a problem-solving version of the Blocks World Task. Both the nature of planning (memory based or display based) and its timing (before or during action) changed with high goal-state access cost (a mouse movement and a 2.5-s delay). In this condition more planning before action was observed, with less planning during action, evidenced by longer first-move latencies, more moves per goal-state inspection, and more short (≤ 0.8 s) and long (>8 s) "preplanned" intermove latencies. Experiment 2 used an eight-puzzle-like transformation task and replicated the effect of goal-state access cost when more complex planning was required, also confirmed by sampled protocol data. Planning before an episode of move making increased with higher goal-state access cost, and planning whilst making moves increased with lower access cost. These novel results are discussed in the context of the soft constraints hypothesis.


Current asthma in schoolchildren is related to fungal spores in classrooms.
The presence of visible mold in households is associated with asthma. However, the role of "classroom fungus" in the development of childhood asthma, as well as the fungal species that may lead to asthma, remains controversial. This nationwide school survey was conducted to investigate the correlation between fungal spores in classrooms and asthma in schoolchildren. From April to May 2011, a cross-sectional survey was conducted to assess allergic/asthmatic conditions in schoolchildren aged 6 to 15 years old in 44 schools across Taiwan. Personal histories and current asthmatic conditions were collected using a modified International Study of Asthma and Allergies in Childhood questionnaire. Fungal spores in classroom were collected using a Burkard Personal Air Sampler and counted under light microscopy. Three-level hierarchical modeling was used to determine the complex correlation between fungal spores in classrooms and childhood asthma. The survey was completed by 6,346 out of 7,154 parents (88.7%). The prevalences of physician-diagnosed asthma, current asthma, and asthma with symptoms reduced on holidays or weekends (ASROH) were 11.7%, 7.5%, and 3.1%, respectively. The geometric mean spore concentrations of total fungi, Aspergillus/Penicillium, and basidiospores were 2,181, 49, and 318 spores/m3. Aspergillus/Penicillium and basidiospores were significantly correlated with current asthma and ASROH after adjusting for personal and school factors. Of those with current asthma, 41% reported relief of symptoms during weekends. Classroom Aspergillus/Penicillium and basidiospores are significantly associated with childhood asthma and ASROH. Government health policy should explore environmental interventions for the elimination of fungal spores in classrooms to reduce the prevalence of childhood asthma.


Superconductivity of the bulk MgB(2)+nano(n)-SiC composite system: a high field magnetization study.
We study the effect of nano(n)-SiC addition on the crystal structure, critical temperature (T(c)), critical current density (J(c)) and flux pinning in MgB(2) superconductors. X-ray diffraction patterns show that all the samples have MgB(2) as the main phase with a very small amount of MgO; further, with n-SiC addition the presence of Mg(2)Si is also noted and confirmed by scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS). The T(c) value for pure MgB(2) is 18.9 K under 8 T applied field, while it is 20.8 K for the 10 wt% n-SiC doped sample under the same field. This points towards the increment in the upper critical field value with n-SiC addition. The irreversibility field (H(irr)) for the 5% n-SiC added sample reached 11.3, 10 and 5.8 T, compared to 7.5, 6.5, and 4.2 T for the pure MgB(2) at 5, 10 and 20 K, respectively. The critical current density (J(c)) for the 5 wt% n-SiC added sample is increased by a factor of 35 at 10 K and 6.5 T field and by a factor 20 at 20 K and 4.2 T field. These results are understood on the basis of superconducting condensate (sigma band) disorder and ensuing intrinsic pining due to B-site C substitution clubbed with further external pinning due to available n-SiC/Mg(2)Si pins in the composite system.


Peritumoral Edema/Tumor Volume Ratio: A Strong Survival Predictor for Posterior Fossa Metastases.
Twenty percent of all brain metastases (BM) occur in the posterior fossa (PF). Radiotherapy sometimes associated with surgical resection remains the therapeutic option, while Karnovsky performance status and graded prognostic assessment (GPA) are the best preoperative survival prognostic factors. To explore the prognostic role of peritumoral brain edema in the PF, which has never been explored though its role in supratentorial BM has been debated. A total of 120 patients diagnosed with PF metastasis who underwent surgical resection were included retrospectively in this analysis. Clinical data were retrieved from electronic patient medical files. The tumor volumes and their associated edema were calculated via manual delineation; subsequently the edema/tumor volume ratio was determined. In multivariate analysis with Cox multivariate proportional hazard model, the edema to tumor volumes ratio (hazard ratio [HR]: 1.727, 95% confidence interval [CI] 1.427-2.083; P < .0001) was identified as a new strong independent prognosis factor on overall survival (OS) whereas edema volume alone was not (P = .469). Moreover, BM complete resection (HR: 0.447, 95% CI 0.277-0.719; P < .001), low (0-1) World Health Organization status at diagnosis (HR: 2.109, 95% CI 1.481-3.015; P < .0001), high GPA class at diagnosis (HR: 1.77, 95% CI 0.9-2.9; P < .04), and postoperative brain irradiation (HR: 2.019, 95% CI 1.213-3.361; P < .007] were all confirmed as independent predictive factors for survival. The edema/tumor ratio appears to greatly influence OS in patients suffering from PF metastases unlike the extent of edema alone. This easily determined as well as strong prognostic factor could be used as an interesting tool in clinical practice to help the management of these patients.


The use of specific antibody in electron microscopy. III. Localization of antigens by the use of unmodified antibody.
Antibody staining was observed in the electron microscope by means of untagged antibody and osmium fixation. The antibody was visualized as a change in morphology due to its deposition on the antigenic structures. Glycerinated chicken breast muscle was stained with antimyosin, anti-H-meromyosin, and antiactin. The staining patterns obtained by electron microscopy were consistent with those previously demonstrated by fluorescence microscopy. A second method was used for confirmation of antibody staining. This consisted of extraction of unstained portions of the sarcomere with 0.6 M potassium iodide, 10(-4)M adenosine triphosphate solution. Stained regions of the sarcomere remained intact because of insolubility of the combined antigen and antibody.


Organization and evolution of brain lipidome revealed by large-scale analysis of human, chimpanzee, macaque, and mouse tissues.
Lipids are prominent components of the nervous system. Here we performed a large-scale mass spectrometry-based analysis of the lipid composition of three brain regions as well as kidney and skeletal muscle of humans, chimpanzees, rhesus macaques, and mice. The human brain shows the most distinct lipid composition: 76% of 5,713 lipid compounds examined in our study are either enriched or depleted in the human brain. Concentration levels of lipids enriched in the brain evolve approximately four times faster among primates compared with lipids characteristic of non-neural tissues and show further acceleration of change in human neocortical regions but not in the cerebellum. Human-specific concentration changes are supported by human-specific expression changes for corresponding enzymes. These results provide the first insights into the role of lipids in human brain evolution.


Differentiating gold nanorod samples using particle size and shape distributions from transmission electron microscope images.
Size and shape distributions of gold nanorod samples are critical to their physico-chemical properties, especially their longitudinal surface plasmon resonance. This interlaboratory comparison study developed methods for measuring and evaluating size and shape distributions for gold nanorod samples using transmission electron microscopy (TEM) images. The objective was to determine whether two different samples, which had different performance attributes in their application, were different with respect to their size and/or shape descriptor distributions. Touching particles in the captured images were identified using a ruggedness shape descriptor. Nanorods could be distinguished from nanocubes using an elongational shape descriptor. A non-parametric statistical test showed that cumulative distributions of an elongational shape descriptor, that is, the aspect ratio, were statistically different between the two samples for all laboratories. While the scale parameters of size and shape distributions were similar for both samples, the width parameters of size and shape distributions were statistically different. This protocol fulfills an important need for a standardized approach to measure gold nanorod size and shape distributions for applications in which quantitative measurements and comparisons are important. Furthermore, the validated protocol workflow can be automated, thus providing consistent and rapid measurements of nanorod size and shape distributions for researchers, regulatory agencies, and industry.


Life transitions in the waning of physical activity from childhood to adult life in the Trois-Rivières study.
Several studies have reported an age-related decline of physical activity (PA). We examined the impact of 4 important transitional periods-adolescence, the beginning of postsecondary education, entry into the labor market, and parenthood-on the PA of participants in the Trois-Rivières quasi-experimental study. In 2008, 44 women and 42 men aged 44.0 ± 1.2 years were given a semistructured interview; the frequency and duration of physical activities were examined during each of these transition periods. Subjects had been assigned to either an experimental program [5 h of weekly physical education (PE) from Grades 1 to 6] or the standard curriculum (40 min of weekly PE) throughout primary school. The percentage of individuals undertaking ≥ 5 h of PA per week decreased from 70.4% to 17.0% between adolescence and midlife. The largest decline occurred on entering the labor market (from 55.9% to 23.4%). At midlife, there were no significant differences of PA level between experimental and control groups. Men were more active than women at each transition except for parenthood. Our results highlight a progressive nonlinear decline of PA involvement in both groups. Promotion initiatives should target these periods to prevent the decline of PA.


Time course for strength and muscle thickness changes following upper and lower body resistance training in men and women.
The purpose of this study was to investigate the time course of skeletal muscle adaptations resulting from high-intensity, upper and lower body dynamic resistance training (WT). A group of 17 men and 20 women were recruited for WT, and 6 men and 7 women served as a control group. The WT group performed six dynamic resistance exercises to fatigue using 8-12 repetition maximum (RM). The subjects trained 3 days a week for 12 weeks. One-RM knee extension (KE) and chest press (CP) exercises were measured at baseline and at weeks 2, 4, 6, 8, and 12 for the WT group. Muscle thickness (MTH) was measured by ultrasound at eight anatomical sites. One-RM CP and KE strength had increased significantly at week 4 for the female WT group. For the men in the WT group, 1 RM had increased significantly at week 2 for KE and at week 6 for CP. The mean relative increases in KE and CP strength were 19% and 19% for the men and 19% and 27% for the women, respectively, after 12 weeks of WT. Resistance training elicited a significant increase in MTH of the chest and triceps muscles at week 6 in both sexes. There were non-significant trends for increases in quadriceps MTH for the WT groups. The relative increases in upper and lower body MTH were 12%-21% and 7%-9% in the men and 10%-31% and 7%-8% in the women respectively, after 12 weeks of WT. These results would suggest that increases in MTH in the upper body are greater and occur earlier compared to the lower extremity, during the first 12 weeks of a total body WT programme. The time-course and proportions of the increase in strength and MTH were similar for both the men and the women.


Self-propagating, molecular-level polymorphism in Alzheimer's beta-amyloid fibrils.
Amyloid fibrils commonly exhibit multiple distinct morphologies in electron microscope and atomic force microscope images, often within a single image field. By using electron microscopy and solid-state nuclear magnetic resonance measurements on fibrils formed by the 40-residue beta-amyloid peptide of Alzheimer's disease (Abeta(1-40)), we show that different fibril morphologies have different underlying molecular structures, that the predominant structure can be controlled by subtle variations in fibril growth conditions, and that both morphology and molecular structure are self-propagating when fibrils grow from preformed seeds. Different Abeta(1-40) fibril morphologies also have significantly different toxicities in neuronal cell cultures. These results have implications for the mechanism of amyloid formation, the phenomenon of strains in prion diseases, the role of amyloid fibrils in amyloid diseases, and the development of amyloid-based nano-materials.


Cellular and humoral immune responses to viral antigens create barriers to lung-directed gene therapy with recombinant adenoviruses.
Recombinant adenoviruses are an attractive vehicle for gene therapy to the lung in the treatment of cystic fibrosis (CF). First-generation viruses deleted of E1a and E1b transduce genes into airway epithelial cells in vivo; however, expression of the transgene is transient and associated with substantial inflammatory responses, and gene transfer is significantly reduced following a second administration of the virus. In this study, we have used mice deficient in immunological effector functions in combination with adoptive and passive transfer techniques to define antigen-specific cellular and humoral immune responses that underlie these important limitations. Our studies indicate that major histocompatibility complex class I-restricted CD8+ cytotoxic T lymphocytes are activated in response to newly synthesized antigens, leading to destruction of virus infected cells and loss of transgene expression. Major histocompatibility complex class II-associated presentation of exogenous viral antigens activates CD4+ T-helper (TH) cells of the TH1 subset and, to a lesser extent, of the TH2 subset. CD4+ cell-mediated responses are insufficient in the absence of cytotoxic T cells to completely eliminate transgene containing cells; however, they contribute to the formation of neutralizing antibodies in the airway which block subsequent adenovirus-mediated gene transfer. Definition of immunological barriers to gene therapy of cystic fibrosis should facilitate the design of rational strategies to overcome them.


Caspase-3 controls AML1-ETO-driven leukemogenesis via autophagy modulation in a ULK1-dependent manner.
AML1-ETO (AE), a fusion oncoprotein generated by t(8;21), can trigger acute myeloid leukemia (AML) in collaboration with mutations including c-Kit, ASXL1/2, FLT3, N-RAS, and K-RAS. Caspase-3, a key executor among its family, plays multiple roles in cellular processes, including hematopoietic development and leukemia progression. Caspase-3 was revealed to directly cleave AE in vitro, suggesting that AE may accumulate in a Caspase-3-compromised background and thereby accelerate leukemogenesis. Therefore, we developed a Caspase-3 knockout genetic mouse model of AML and found that loss of Caspase-3 actually delayed AML1-ETO9a (AE9a)-driven leukemogenesis, indicating that Caspase-3 may play distinct roles in the initiation and/or progression of AML. We report here that loss of Caspase-3 triggers a conserved, adaptive mechanism, namely autophagy (or macroautophagy), which acts to limit AE9a-driven leukemia. Furthermore, we identify ULK1 as a novel substrate of Caspase-3 and show that upregulation of ULK1 drives autophagy initiation in leukemia cells and that inhibition of ULK1 can rescue the phenotype induced by Caspase-3 deletion in vitro and in vivo. Collectively, these data highlight Caspase-3 as an important regulator of autophagy in AML and demonstrate that the balance and selectivity between its substrates can dictate the pace of disease.


A GRASP55-rab2 effector complex linking Golgi structure to membrane traffic.
Membrane traffic between the endoplasmic reticulum (ER) and Golgi apparatus and through the Golgi apparatus is a highly regulated process controlled by members of the rab GTPase family. The GTP form of rab1 regulates ER to Golgi transport by interaction with the vesicle tethering factor p115 and the cis-Golgi matrix protein GM130, also part of a complex with GRASP65 important for the organization of cis-Golgi cisternae. Here, we find that a novel coiled-coil protein golgin-45 interacts with the medial-Golgi matrix protein GRASP55 and the GTP form of rab2 but not other Golgi rab proteins. Depletion of golgin-45 disrupts the Golgi apparatus and causes a block in secretory protein transport. These results demonstrate that GRASP55 and golgin-45 form a rab2 effector complex on medial-Golgi essential for normal protein transport and Golgi structure.


Effects of endurance training on glucose tolerance and plasma lipid levels in older men and women.
Eleven healthy men and women (63 +/- 1 years) participated in a 12-month endurance-training program to determine the effects of low-intensity and high-intensity training on glucose tolerance and plasma lipids in older persons. Plasma glucose, insulin, and C-peptide concentrations were measured for three hours after ingestion of 100 g of glucose and the total areas under the respective curves were calculated. Total plasma lipids and lipoprotein concentrations were determined during fasting. Maximal oxygen uptake increased 12% during six months of low-intensity training; a further 18% increase occurred during an additional six months of high-intensity training. Glucose tolerance, which was normal initially, was not significantly changed after training. However, the total area for insulin was 8% lower after low-intensity training, and 23% lower after high-intensity training, compared with before training. C-peptide concentrations were similarly reduced. Plasma lipid and lipoprotein concentrations were unchanged after low-intensity training, but high-intensity training resulted in an increase in high-density lipoprotein cholesterol and a reduction in triglycerides. These results demonstrate that older persons respond to prolonged, high-intensity endurance training with an increase in sensitivity to insulin and a favorable alteration in their plasma lipoprotein-lipid profile.


Daily consumption of the collagen supplement Pure Gold Collagen® reduces visible signs of aging.
With age, changes in the metabolic processes of structural components of the skin lead to visible signs of aging, such as increased dryness and wrinkle formation. The nutritional supplement, Pure Gold Collagen(®), which consists of hydrolyzed collagen, hyaluronic acid, vitamins, and minerals, was developed to counteract these signs. An open-label study was conducted to investigate the effects of this nutritional supplement on skin properties. Supplementation with 50 mL of Pure Gold Collagen on a daily basis for 60 days led to a noticeable reduction in skin dryness, wrinkles, and nasolabial fold depth. In addition, a significant increase in collagen density and skin firmness was observed after 12 weeks. The data from this study suggest that Pure Gold Collagen can counteract signs of natural aging.


Mesoporous TiO(2): comparison of classical sol-gel and nanoparticle based photoelectrodes for the water splitting reaction.
This paper describes a systematic comparison of the photoelectrochemical properties of mesoporous TiO(2) films prepared by the two most prevalent templating methods: The use of preformed, crystalline nanoparticles is generally considered advantageous compared to the usage of molecular precursors such as TiCl(4), since the latter requires a separate heat treatment at elevated temperature to induce crystallization. However, our photoelectrochemical experiments clearly show that sol-gel derived mesoporous TiO(2) films cause an about 10 times higher efficiency for the water splitting reaction than their counterparts obtained from crystalline TiO(2) nanoparticles. This result indicates that for electrochemical applications the performance of nanoparticle-based metal oxide films might suffer from insufficient electronic connectivity.


Morphostasis in a novel eukaryote illuminates the evolutionary transition from phagotrophy to phototrophy: description of Rapaza viridis n. gen. et sp. (Euglenozoa, Euglenida).
Morphostasis of traits in different species is necessary for reconstructing the evolutionary history of complex characters. Studies that place these species into a molecular phylogenetic context test hypotheses about the transitional stages that link divergent character states. For instance, the transition from a phagotrophic mode of nutrition to a phototrophic lifestyle has occurred several times independently across the tree of eukaryotes; one of these events took place within the Euglenida, a large group of flagellates with diverse modes of nutrition. Phototrophic euglenids form a clade that is nested within lineages of phagotrophic euglenids and that originated through a secondary endosymbiosis with green algae. Although it is clear that phototrophic euglenids evolved from phagotrophic ancestors, the morphological disparity between species representing these different nutritional modes remains substantial. We cultivated a novel marine euglenid, Rapaza viridis n. gen. et sp. ("green grasper"), and a green alga, Tetraselmis sp., from the same environment. Cells of R. viridis were comprehensively characterized with light microscopy, SEM, TEM, and molecular phylogenetic analysis of small subunit rDNA sequences. Ultrastructural and behavioral observations demonstrated that this isolate habitually consumes a specific strain of Tetraselmis prey cells and possesses a functional chloroplast that is homologous with other phototrophic euglenids. A novel feeding apparatus consisting of a reduced rod of microtubules facilitated this first and only example of mixotrophy among euglenids. R. viridis also possessed a robust photoreception apparatus, two flagella of unequal length, euglenoid movement, and a pellicle consisting of 16 strips and one (square-shaped) whorl of posterior strip reduction. The molecular phylogenetic data demonstrated that R. viridis branches as the nearest sister lineage to phototrophic euglenids. The unusual combination of features in R. viridis combined with its molecular phylogenetic position completely conforms to the expected transitional stage that occurred during the early evolution of phototrophic euglenids from phagotrophic ancestors. The marine mixotrophic mode of nutrition, the preference for green algal prey cells, the structure of the feeding apparatus, and the organization of the pellicle are outstanding examples of morphostasis that clarify pivotal stages in the evolutionary history of this diverse group of microbial eukaryotes.


Tunable terahertz reflection of graphene via ionic liquid gating.
We report a highly efficient tunable THz reflector in graphene. By applying a small gate voltage (up to ±3 V), the reflectance of graphene is modulated from a minimum of 0.79% to a maximum of 33.4% using graphene/ionic liquid structures at room temperature, and the reflection tuning is uniform within a wide spectral range (0.1-1.5 THz). Our observation is explained by the Drude model, which describes the THz wave-induced intraband transition in graphene. This tunable reflectance of graphene may contribute to broadband THz mirrors, deformable THz mirrors, variable THz beam splitters and other optical components.


Lipopolysaccharide exposure during the early postnatal period adversely affects the structure and function of the developing rat carotid body.
The carotid body (CB) substantially influences breathing in premature infants by affecting the frequency of apnea and periodic breathing. In adult animals, inflammation alters the structure and chemosensitivity of the CB, yet it is not known if this pertains to neonates. We hypothesized that early postnatal inflammation leads to morphological and functional changes in the developing rat CB, which persists for 1 wk after the initial provoking insult. To test our hypothesis, we exposed rat pups at postnatal day 2 (P2) to lipopolysaccharide (LPS; 100 μg/kg) or saline (SAL) intraperitoneally. At P9-10 (1 wk after treatment), LPS-exposed animals had significantly more spontaneous intermittent hypoxic (IH) events, attenuated ventilatory responses to changes in oxygen tension (measured by whole body plethysmography), and attenuated hypoxic chemosensitivity of the carotid sinus nerve (measured in vitro), compared with SAL-exposed controls. These functional changes were associated with the following: 1) increased inflammatory cytokine mRNA levels; 2) decreased volume of supportive type II cells; and 3) elevated dopamine levels (a major inhibitory neuromodulator) within the CB. These findings suggest that early postnatal inflammation in newborn rats adversely affects the structure and function of the CB and is associated with increased frequency of intermittent desaturations, similar to the phenomenon observed in premature infants. Furthermore, this is the first newborn model of spontaneous intermittent desaturations that may be used to understand the mechanisms contributing to IH events in newborns.


PCR - the polymerase chain reaction.
DNA-based procedures are becoming increasingly common within the analytical laboratory where the polymerase chain reaction (PCR) has become an indispensable technique. Developed in 1985 by Kary B. Mullis, PCR revolutionized the way that deoxyribonucleic acid (DNA) could be copied. Mullis's invention allowed researchers to make millions of copies of a selected DNA region within hours. Today, PCR can take minutes. PCR has widespread analytical applications in the food, environmental, medical and forensic fields. This Technical Brief covers the basics of PCR and some of its variations.


Equine-like G3 rotavirus in Hungary, 2015 - Is it a novel intergenogroup reassortant pandemic strain?
Novel, intergenogroup reassortant G3 rotavirus strains are spreading in at least three continents: Asia, Australia, and Europe. The present study provides evidence that a closely related G3P[8] strain circulated in Hungary during 2015. Whole genome sequencing and phylogenetic analysis showed that the identified strain continues to evolve by reassortment. This observation demonstrates the genomic plasticity of the novel strain, which is thought to be a prerequisite of the success of emerging rotavirus genotypes.


Optical content-addressable parallel processor: architecture, algorithms, and design concepts.
Associative processing based on content-addressable memories has been argued to be the natural solution for nonnumerical information processing applications. Unfortunately, the implementation requirements of these architectures when one uses conventional electronic technology have been cost prohibitive; therefore associative processors have not been realized. Instead, software methods that emulate the behavior of associative processing have been promoted and mapped onto conventional locationaddressable systems. However, this does not bring about the natural parallelism of associative processing, namely, the ability to access many data words simultaneously. Optics has the advantage over electronics of directly supporting associative processing by providing economic and efficient interconnects, massive parallelism, and high-speed processing. The principles of designing an optical content-addressable parallel processor (OCAPP) for the efficient support of parallel symbolic computing are presented. The architectu re is designed to exploit optics advantages fully in interconnects and high-speed operations. Several parallel search-and-retrieval algorithms are mapped onto an OCAPP to illustrate its capability of supporting parallel symbolic computing. A theoretical performance analysis of these algorithms is presented. This analysis reveals that the execution times of the parallel algorithms presented are independent of the problem size, which makes the OCAPP suitable for applications in which the number of data sets to be operated on is high (e.g., massive parallel processing). A preliminary optical implementation of the architecture with currently available optical components is also presented.


Methylglyoxal-derived hydroimidazolone residue of plasma protein can behave as a predictor of prediabetes in Spontaneously Diabetic Torii rats.
Prediabetes, typically defined as impaired glucose tolerance and/or impaired fasting blood glucose, is a high-risk state of developing diabetes. The association of diabetes-related metabolites with prediabetes has not been investigated intensively. This study aimed to get insights into the metabolic behaviors of some typical diabetes-related metabolites in plasma of male Spontaneously Diabetic Torii (SDT) rats during pathogenic progress of diabetes and to assess in vivo if the variation in these metabolites related to the progression of prediabetic stage. To address this question, SDT rats and Sprague Dawley (SD) rats as control were maintained from the age of 7 to 25 weeks. Five typical advanced glycation end products (AGEs) residue of plasma protein and their free adducts were determined by liquid chromatography with tandem mass detection over the duration of the investigation. The SDT rats exhibited impaired glucose tolerance since the age of 12 weeks and developed diabetes with significantly elevated fasting glucose levels after 22 weeks. At the prediabetic stage (12-21 weeks), no significant differences were observed on AGE-free adducts levels of SDT rats compared with SD rats. However, methylglyoxal-derived hydroimidazolone (MG-H1) residue contents of plasma protein were significantly elevated in SDT rats at the age of 16 weeks, whereas other AGE residues of plasma protein did not show marked difference. The present study has revealed significant increase in MG-H1 residue content of plasma protein at the prediabetic stage of a spontaneously diabetic rat model, irrespective of unaltered fasting blood glucose and constant plasma levels of other AGEs.


Glutamine enhances the gut-trophic effect of growth hormone in rat after massive small bowel resection.
Background. Bowel-specific nutrient, glutamine, growth hormone, and modified diet have been reported to jointly improve nutrient absorption in patients with short bowel syndrome. However, controversy exists about the exact treatment factor. In this study we attempted to analyze the individual and combined effect of glutamine supplementation and growth hormone on small bowel adaptation by using tube feeding to control luminal nutrition supply. Materials and methods. Thirty-two adult male Sprague-Dawley rats (278 +/- 8 g) underwent 85% mid-small bowel resection and were randomly assigned to four groups: Control, receiving control liquid diet via a gastrotomy tube; GLN, receiving liquid diet enriched with 20 g. L(-1) glutamine; GH, receiving subcutaneous growth hormone (GH) (0.3 IU, bid); and GLN + GH, receiving both glutamine supplementation and GH treatment. All animals were provided with isocaloric (60 kcal/day) and isonitrogenous (0.686 g/day) nutrition. Absorption tests were performed in the form of oral nutrient tests with (14)C-labeled glucose and (3)H-labeled palmitic acid on the Postoperative Day 12. Results. GH treatment significantly increased the plasma insulin-like growth factor I (IGF-I) level, body weight, jejunal and ileal villous height and mucosal thickness, and peak plasma (14)C and (3)H levels. Glutamine supplementation did not produce a significant difference; however, combined with GH treatment, glutamine supplementation further increased body weight, plasma IGF-I level, jejunal and ileal villous height and mucosal thickness, and peak plasma (14)C and (3)H levels significantly. Conclusions. After massive small bowel resection, enteral glutamine supplementation alone has no remarkable beneficial effect on bowel adaptation. However, glutamine supplementation enhanced the gut-trophic effect of GH.


ACRE: Absolute concentration robustness exploration in module-based combinatorial networks.
To engineer cells for industrial-scale application, a deep understanding of how to design molecular control mechanisms to tightly maintain functional stability under various fluctuations is crucial. Absolute concentration robustness (ACR) is a category of robustness in reaction network models in which the steady-state concentration of a molecular species is guaranteed to be invariant even with perturbations in the other molecular species in the network. Here, we introduce a software tool, absolute concentration robustness explorer (ACRE), which efficiently explores combinatorial biochemical networks for the ACR property. ACRE has a user-friendly interface, and it can facilitate efficient analysis of key structural features that guarantee the presence and the absence of the ACR property from combinatorial networks. Such analysis is expected to be useful in synthetic biology as it can increase our understanding of how to design molecular mechanisms to tightly control the concentration of molecular species. ACRE is freely available at https://github.com/ramzan1990/ACRE.


Are there separate ON and OFF channels in fly motion vision?
Visual information is processed in a series of subsequent steps. The performance of each of these steps depends not only on the computations it performs itself but also on the representation of the visual surround on which it operates. Here we investigate the consequences of signal preprocessing for the performance of the motion-detection system of the fly. In particular, we analyze whether the retinal input signals are rectified and segregate into separate ON and OFF channels, which then feed independent parallel motion-detection pathways. We recorded the activity of an identified directionally selective interneuron (H1-cell) in response to apparent motion stimuli, i.e. sequential brightness changes at two neighboring locations in the visual field, as well as to brightness changes at only a single location. For apparent motion stimuli, the motion-dependent response component was determined by subtracting from the overall response to the individual stimulus components when presented alone. The following conclusions could be derived: (1) Apparent motion consisting of a sequence of increased or decreased brightness at two locations in the visual field have the same optimum interstimulus time interval (Fig. 3). (2) Sequences of brightness steps of like polarity (either increments or decrements) elicit positive and negative motion-dependent response components when mimicking motion in the cell's preferred and null direction, respectively. The motion-dependent response components are inverted in sign when the brightness steps of a stimulus sequence have a different polarity (Fig. 7). (3) The responses to the beginning and the end of a brightness pulse depend on the pulse duration. For pulse durations of less than 2 s, both events interact with each other (Fig. 9). All of these results do not provide any indication that the fly processes motion information in independent ON and OFF motion detectors. Brightness changes of both signs are rather represented at the input of the same movement detectors, and interactions between signals resulting from both brightness increments and decrements take their sign into account. This type of preprocessing of the retinal input is argued to render a motion-detection system particularly robust against noise.


Chronic salicylate poisoning and severe malaria.
BACKGROUND Salicylates continue to be marketed and to be used in developing countries as over-the-counter (OTC) antipyretics in children, whereas in developed countries they are no longer used in children because of safety concerns. The presenting signs of salicylate poisoning, especially chronic (repeated administration of therapeutic or excessive doses for longer than 12 h), can include metabolic acidosis, hypoglycaemia, lethargy, and coma and fits. These signs are also common in severe malaria in African children. Admission of two probable cases of chronic salicylate poisoning prompted us to look for other cases among children presenting to our hospital in Kenya, apparently with severe malaria. METHODS All children admitted to Kilifi District Hospital between July and September, 1994, who had a positive blood film for Plasmodium falciparum, and one or more of coma, prostration, or respiratory distress were eligible. As well as routine tests for malaria and routine biochemistry, salicylate concentrations were measured. Management of children (aged 6 months to 10 years) in the community was assessed by a cross-sectional survey of 463 households and by interviews with mothers 2 days after they had bought OTC drugs for a child with fever. FINDINGS Data were available for 143 of 154 children with initial primary diagnoses of severe malaria. 129 (90 percent) had detectable (>l mg/dL) salicylate. Six of these had salicylate concentrations of 20 mg/dL or higher. All six had neurological impairment and metabolic acidosis and four were, or became, hypoglycaemic. OTC drugs were the first-line treatment in 188 (74 percent) of 254 fever episodes during the 2 weeks before the cross-sectional survey. Of 250 mothers who bought drugs for a febrile child, 236 (94 percent) bought a preparation containing salicylates and 50 (21 percent) gave a dose higher than the manufacturer's recommended maximum. INTERPRETATION These cases suggest that in some children salicylate poisoning may cause or contribute to the development of metabolic acidosis and hypoglycaemia, complications of severe malaria associated with high mortality.


Pediatric mastocytosis-associated KIT extracellular domain mutations exhibit different functional and signaling properties compared with KIT-phosphotransferase domain mutations.
Compared with adults, pediatric mastocytosis has a relatively favorable prognosis. Interestingly, a difference was also observed in the status of c-kit mutations according to the age of onset. Although most adult patients have a D(816)V mutation in phosphotransferase domain (PTD), we have described that half of the children carry mutations in extracellular domain (ECD). KIT-ECD versus KIT-PTD mutants were introduced into rodent Ba/F3, EML, Rat2, and human TF1 cells to investigate their biologic effect. Both ECD and PTD mutations induced constitutive receptor autophosphorylation and ligand-independent proliferation of the 3 hematopoietic cells. Unlike ECD mutants, PTD mutants enhanced cluster formation and up-regulated several mast cell-related antigens in Ba/F3 cells. PTD mutants failed to support colony formation and erythropoietin-mediated erythroid differentiation. ECD and PTD mutants also displayed distinct whole-genome transcriptional profiles in EML cells. We observed differences in their signaling properties: they both activated STAT, whereas AKT was only activated by ECD mutants. Consistently, AKT inhibitor suppressed ECD mutant-dependent proliferation, clonogenicity, and erythroid differentiation. Expression of myristoylated AKT restored erythroid differentiation in EML-PTD cells, suggesting the differential role of AKT in those mutants. Overall, our study implied different pathogenesis of pediatric versus adult mastocytosis, which might explain their diverse phenotypes.


Biologic characteristics of premalignant breast disease.
Breast cancer is the second leading cause of cancer death in women in the United States. While mammography and breast magnetic resonance imaging (MRI) improve detection of early disease, there remains an unmet need for biomarkers for risk stratification, early detection, prediction, and disease prognosis. A number of early breast lesions, from atypical hyperplasias to carcinomas in situ, are associated with an increased risk of developing subsequent invasive breast carcinoma. The recent development of genomic, epigenomic, and proteomic tools for tissue biomarker detection, including array CGH, RNA expression microarrays, and proteomic arrays have identified a number of potential biomarkers that both identify patients at increased risk, as well as provided insights into the pathology of early breast cancer development. This chapter focuses on the detection and application of tissue and serum biomarkers for the identification and risk stratification of early breast cancer lesions.


Predicting pharmacy costs and other medical costs using diagnoses and drug claims.
Predicting health care costs for individuals and populations is essential for managing care. However, the comparative power of diagnostic and drug data for predicting future costs has not been closely examined. We sought to compare the predictive performance of claims-based models using diagnoses, drugs claims, and combined data to predict health care costs. More than 1 million commercially insured, nonelderly individuals in a national (MEDSTAT MarketScan) research database comprised our sample. We used 1997 and 1998 drug and diagnostic profiles to predict costs in 1998 and 1999, respectively. To assess model performance, we compared R2 values and predictive ratios (predicted costs/actual costs) for important subgroups. Models using both drug and diagnostic data best predicted subsequent-year total health care costs (highest R2 = 0.168 versus 0.116 and 0.146 for models based on drug or diagnostic data alone, respectively), with highly accurate predictive ratios (0.95-1.05) for subgroups of patients with major medical conditions. Models predicting pharmacy costs had substantially higher R2 values than models predicting other medical costs (highest R2 0.493 versus 0.124). Drug-based models predicted future pharmacy costs better than diagnosis-based models (highest R2 = 0.482 versus 0.243), whereas diagnosis-based models predicted total costs (highest R2 = 0.146 versus 0.116) and nonpharmacy costs (highest R2 = 0.116 versus 0.071) more effectively than drug-based models. Newer models had markedly higher R values than older ones, largely because of richer data rather than model refinements. Combined drug and diagnostic data predicts total health care costs better than either type of data alone. Pharmacy spending is particularly predictable from drug data, whereas diagnoses are more useful than drugs for predicting other medical costs and total costs. Using even slightly more recent data can substantially boost model performance measures; thus, model comparisons should be conducted on the same dataset.


Resolution and sensitivity of the eyes of the Asian honeybees Apis florea, Apis cerana and Apis dorsata.
Bees of the genus Apis are important foragers of nectar and pollen resources. Although the European honeybee, Apis mellifera, has been well studied with respect to its sensory abilities, learning behaviour and role as pollinators, much less is known about the other Apis species. We studied the anatomical spatial resolution and absolute sensitivity of the eyes of three sympatric species of Asian honeybees, Apis cerana, Apis florea and Apis dorsata and compared them with the eyes of A. mellifera. Of these four species, the giant honeybee A. dorsata (which forages during moonlit nights) has the lowest spatial resolution and the most sensitive eyes, followed by A. mellifera, A. cerana and the dwarf honeybee, A. florea (which has the smallest acceptance angles and the least sensitive eyes). Moreover, unlike the strictly diurnal A. cerana and A. florea, A. dorsata possess large ocelli, a feature that it shares with all dim-light bees. However, the eyes of the facultatively nocturnal A. dorsata are much less sensitive than those of known obligately nocturnal bees such as Megalopta genalis in Panama and Xylocopa tranquebarica in India. The differences in sensitivity between the eyes of A. dorsata and other strictly diurnal Apis species cannot alone explain why the former is able to fly, orient and forage at half-moon light levels. We assume that additional neuronal adaptations, as has been proposed for A. mellifera, M. genalis and X. tranquebarica, might exist in A. dorsata.


COVID-19: An up-to-date review - from morphology to pathogenesis.
The entire world is under a devastating pandemic caused by COVID-19 with a high mortality rate. Knowledge of the viral structure, factors that help in its progression and spread, pathological findings, diagnostic methods and, treatment modalities helps in understanding the viral disease and also in treating the patients in a better way besides preventing the community spread of this deadly infection. The causative agent is a single- stranded RNA virus. The clinical spectrum varies in symptomatic and asymptomatic patients, who later become potential silent carriers, thus unknowingly spreading the virus. The virus constantly undergoes recombination, with reports of cross-species infections. Studies have indicated a strong immunological basis of COVID-19 infection. Not only does it weaken the immune system causing multi-organ involvement but also helps in its progression and spread to others.Multiple organs especially lungs, heart, kidney, gastrointestinal and hepatic system, brain and skin are affected varying in their severity. Similarly, persons with associated co-morbidities are likely to be affected more in terms of the number as well as in the severity. Real- time reverse transcription polymerase chain reaction confirms the presence of COVID-19 infection. Serological diagnosis helps in diagnosing an ongoing outbreak or retrospective infection. Furthermore, it also identifies individuals who have been infected or have recovered from the disease especially the asymptomatic. This helps in the development of an effective vaccine indicating the status of herd immunity in the community. Different treatment modalities are being tried and under trial. This review article thus highlights the global epidemiological status, characteristic of the virus, symptomatology of the patients, role of diagnostic tests available, organs affected including their morphological changes and the latest line of treatment of COVID-19.